Nephrol Dial Transplant (2006) 21: 811–812
doi:10.1093/ndt/gfi338
Advance Access publication 22 December 2005
Nephroquiz
(Section Editor: M. G. Zeier)
Recurrent paroxysms of metabolic acidosis in
a haemodialysis patient
Case
A 56-year-old haemodialysis patient was observed
to have a substantial metabolic acidosis prior to a
routine haemodialysis treatment. She had developed
chronic renal failure and become dialysis-dependent
10 years earlier. A renal transplant had failed; she had
peripheral vascular disease, and had decreased cardiac
function because of a suspected cardiomyopathy.
Otherwise, she was stable.
The patient voiced no complaints. However, her pH
was 7.146, PaO2 124 mmHg, PaCO2 27 mmHg, and
HCO3 9 mmol/l. The serum Naþ was normal and the
serum Cl was elevated, commensurate with the HCO
3
decrease indicating that the anion gap was unchanged.
She was haemodialyzed for 5 h against a 35 mmol/l
HCO
3 -containing dialysate without incident. At
the end of the treatment, the pH was 7.41, PaO2
120 mmHg, PaCO2 34 mmHg, and the HCO
3 was
22 mmol/l. We were puzzled as to what was going on.
Thereafter, her acid–base status was variable. The
values remained normal until one month later, when
she entered the dialysis unit with a pH of 7.07, with
corresponding PaCO2 20 mmHg and HCO
3 of 5 mmol/l.
Again, the Cl was elevated while the anion gap
remained unchanged. Again, a high HCO
3 dialysate
rectified the situation. We remained perplexed. On other
occasions, the hyperchloraemic metabolic acidosis was
not as severe. Detailed questioning of the patient revealed nothing out of the ordinary. On another occasion,
about six months after the episodes had begun, she
again came in with a pH of 7.08, PaCO2 27 mmHg,
and HCO
3 6 mmol/l. We remained puzzled while she
appeared no more the worse for wear. The episodes
continued for several more weeks until we finally
asked her to bring in any or all items she might be
ingesting.
Perhaps you are cleverer than we were and can
make the diagnosis without inspecting the items the
patient brought with her?
The patient was taking a traditional German cough
medicine SalmixÕ . Each lozenge contains 30 mg Succus
liquiritiae, also known as Glycyrrhiza glabra, and
20 mg NH4Cl (Figure 1). As the name implies, the
compound contains glycyrrhizinic acid; however, licoCorrespondence and offprint requests to: Friedrich C. Luft, Franz
Volhard Clinic, Wiltberg Strasse 50, 13125 Berlin, Germany.
Email: [email protected]
rice poisoning did not appear to be the problem here.
The manufacturer claims the material is indicated
for the treatment of cough and catarrh. She admitted
to consuming 100 g of lozenges during each interdialytic interval, easily enough to explain the profound
metabolic acidosis in the face of no renal function.
We thought that this bizarre poisoning with overthe-counter (OTC) preparations might be a European
phenomenon and were therefore interested in the
report by Wong et al. [1]. These investigators described
a patient with normal renal function, who entered
the hospital with a pH of 7.19, PaO2 115, PaCO2 32
(both mmHg) and HCO
3 12 mmol/l. That patient
had a slightly elevated anion gap and a serum K of
2.7 mmol/l. The authors reported on phensedyl, a
proprietary cough remedy available without prescription in Hong Kong. The material contains various
ingredients; including NH4Cl. NH4Cl is a common
component of many antitussives. For example, 5 ml
of Benylin ExpectorantÕ , a common cough remedy
marketed in North America, contains 135 mg NH4Cl
in 5 ml of the compound. Megarbane et al. [2] reported
on NH4Cl poisoning in an elderly patient who was
prescribed the material by her physician. The patient
recovered from hyperchloraemic metabolic acidosis
despite an admission pH of 6.9. The reasons for this
therapeutic misadventure were not stated.
One of the authors (Luft) organized and participated
in an investigation of Naþ/Hþ exchange in human
lymphocytes and platelets in chronic and subacute
metabolic acidosis [3]. The subjects ingested 15 g
NH4Cl for five days. Their pH decreased from 7.40 to
7.26. Cl increased from 103 to 116 mmol/l, HCO
3
decreased from 27 to 13 mmol/l. Body weight fell 2 kg,
while plasma renin activity and plasma aldosterone increased substantially. Urinary Kþ losses were
increased. Naþ/Hþ exchange in lymphocytes was
stimulated. Luft remembers feeling awful during the
experiments. He recalls that his father, a German
Himalayan climber from the 1930s, related that
NH4Cl was used as a strategy above 6000 m to
combat respiratory alkalosis and high altitude sickness
[4]. The strategy was a failure. This report is the first
to our knowledge of NH4Cl poisoning in a dialysis
patient. Clearly, her lack of renal function made the
clinical picture more dramatic and that much more
puzzling.
Diagnosis: Metabolic acidosis from NH4Cl poisoning through an OTC cough medicine.
ß The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
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812
J. B. Lüth and F. C. Luft
Fig. 1. SalmixÕ package and lozenges are shown. Each lozenge contains 20 mg NH4Cl. About 500 of these lozenges in each interdialytic
period would amount to 10 g NH4Cl.
Conflict of interest statement. The authors deny any conflicts
of interest. They do not hold stock in the company which
manufactures of SalmixÕ .
4. Luft UC. Die Höhenanpassung. Ergebnisse der Physiologie,
biologischen Chemie und experimentellen Pharmakologie. In:
Ascher L, Spiro K, eds. Verlag von J.F. Bergmann, Münich,
Germany, 1941: 257–313
References
1. Wong KM, Chak WL, Cheung CY et al. Hypokalemic
metabolic acidosis attributed to cough mixture abuse. Am J
Kidney Dis 2001; 38: 390–394
2. Megarbane B, Bruneel F, Bedos JP, Regnier B. Ammonium
chloride poisoning: a misunderstood cause of metabolic acidosis
with normal anion gap. Intens Care Med 2000; 26: 1869
3. Reusch HP, Reusch R, Rosskopf D, Siffert W, Mann JF,
Luft FC. Naþ/Hþ exchange in human lymphocytes and platelets
in chronic and subacute metabolic acidosis. J Clin Invest 1993;
92: 858–865
Johann B. Lüth1
Friedrich C. Luft2
1
Gemeinschaftspraxis und
Dialysezentrum Hannover
2
Medical Faculty of the Charite´
Franz Volhard Clinic HELIOS
Klinikum-Berlin
Germany